Interplay between Xeroderma Pigmentosum Complimentary Group D and Multiple Drug Resistance 1 Genes (XPD and MDR1) in Relation to Prostate Cancer Risk

Abstract

Prostate cancer (PCA) detection could be improved by identifying genetic susceptibility markers within essential biological pathways. This study evaluated the individual and joint modifying effects of 2 highly variant genes (MDR1 and XPD) in relation to PCA risk within a large and unique case‐control study. We hypothesize men possessing two or more high‐risk XPD 312Asn alone or combined with MDR1 3435T alleles have an increased risk of developing PCA, due to decreased capacity to repair DNA damage or eliminate exogenous compounds. Genetic alterations detected in germ‐line DNA collected from 220 incident PCA cases and 698 healthy age matched controls were assessed using TaqMan real‐time PCR. Gene‐gene interaction was analyzed by LR analysis models. A 1.4‐6‐fold increase was observed in PCA risk among carriers with 1 or more high‐risk XPD 312Asn alleles alone or combined with at least one slow MDR1 3435T alleles. This study showed variant XPD alone or combined with polymorphic MDR1 modify PCA susceptibility among AA men. Future studies will evaluate an important panel of genetic susceptibility biomarkers for detection within high‐risk populations. Bales Medical Research Fund